Iliac crest needle biopsy as a method for determining estrogen receptors in bone metastases from breast cancer

The purpose of our study was to clarify whether the amount of tissue extracted by means of iliac crest needle biopsy (ICNB) would suffice for a quantitative determination of estrogen receptors (ER) in bone metastases, and to see if the method currently used for determining ER in primary tumors could also be successfully utilized in ICNB. 22 of 31 breast cancer patients examined could be evaluated. ER was positive in 7 (31.8%). Reasonable data are to be expected when the biopsy weight exceeds 0.1 g. Our study confirms that the necessary amount of tissue for ER analysis can indeed be extracted by ICNB. Our results justify further studies on a larger group of patients, since we cannot make conclusive statements concerning the value of this method for predicting the ultimate success of an endocrine treatment.     

Occupational medicine analysis and evaluation of spinal load in the mining process

The calculations of the spinal column loading of miners are based on working time studies in operations with predominantly physical heavy work and elevated mechanical load. An elaborated model for the mining of ores, the applicability to underground workers and the comparability of loading quantities, based on the dosage measurement, are described.     

Eicosanoide und Phospholipasen

Summary Prostaglandins, thromboxanes, and leukotrienes have been implicated to play an important role in physiology as well as in a growing list of pathophysiologic conditions. These oxidation products of 8.11.14.-eicosatrienoic-,5.8.11.14.-eicosatetraenoic-, and 5.8.11.14.17.-pentaenoic acids have been collectively designated eicosanoids. Many clinically important diseases are associated with altered eicosanoid biosynthesis. Furthermore, a series of hormones are known to induce acutely formation of eicosanoids, suggesting a crucial role in a multitude of tissue responses including phenomena such as secretion, platelet aggregation, chemotaxis, and smooth muscle contraction. The major precursor for the eicosanoids seems to be 5.8.11.14.-eicosatetraneoic acid or arachidonic acid. Virtually all of arachidonic acid however is present in esterified form in complex glycerolipids. Since cyclooxygenase and the lipoxygenases utilize arachidonic acid in its free form, a set of acylhydrolases is required to liberate arachidonic acid from membrane lipids before eicosanoid formation can occur. It became only recently apparent that a minor acidic phospholipid, phosphatidylinositol, comprising only 5%–10% of the phospholipid mass in mammalian cells, plays an important role in arachidonic acid metabolism. Phosphatidylinositol — after phosphorylation to phosphatidylinositolphosphate and phosphatidylinositolbisphosphate — appears to be hydrolyzed by specific phospholipases C generating 1-stearoyl-2-arachidonoyl-diglyceride. Diglyceride serves as substrate for diglyceride lipase to form monoglyceride and free fatty acid. Alternatively diglyceride is phosphorylated by diglyceride kinase yielding phosphatidic acid, which is believed to be reincorporated into phosphatidylinositol. In addition to phosphatidylinositol phosphatidylcholine, phosphatidylethanolamine and phosphatidic acid may contribute to arachidonic acid release. These phospholipids are substrates for phospholipases A₂ generating free arachidonic acid and the respective lysophospholipid. Understanding of the biochemistry of arachidonic acid liberation may be critical in developing strategies of pharmacological intervention in a variety of pathological conditions.

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Abkürzungen AA Arachidonsäure - CDP-DG Cytidindiphosphodiglycerid - DG Diglycerid - DPI Phosphatidylinositoldiphosphat - FA freie Fettsäure - GSH Glutathion - HETE Hydroxyeicosatetraensäure - HPETE Hydroperoxyeicosatetraensäure - MDA Malondialdehyd - MG Monoglycerid - MI Myoinositol - Lyso-PA Lysophosphatidsäure - Lyso-PC Lysophosphatidylcholin - Lyso-Pl Lysophosphatidylinositol - LT Leukotrien - PA Phosphatidsäure - PC Phosphatidylcholin - PG Prostaglandin - Pl Phosphatidylinositol - THETE Tetrahydroxyeicosatetraensäure - TX Thromboxan Diese Arbeit wurde von der Deutschen Forschungsgemeinschaft (HA-1083/2-2) und dem Forschungsrat Rauchen und Gesundheit (Hamburg) unterstütztHerrn Professor Hans Neurath zum 75. Geburtstag gewidmet     

武汉地区工人与联邦德国工人冠心病危险因素的比较

我国心肌梗塞的发病率和死亡率明显低于联邦德国。为了比较两国工人之间的冠心病危险因素,我们和海德堡大学协作,对2146名中国工人进行了调查。中国工人血清总胆固醇水平(155.0mg/dl)明显低于联邦德国工人。降低的部分是致动脉硬化的低密度脂蛋白胆固醇(LDL-C)和极低密度脂蛋白胆固醇(VLDL-C)。而有保护作用的高密度脂蛋白胆固醇水平高于联邦德国工人。因而LDL-C/HDL-C的比值明显小于联邦德国工人。中国工人载脂蛋白B(apoB)和apoB/apoAI的比值明显低于联邦德国工人。这可能是我国冠心病发病率低的重要原因。中国人每天摄入的胆固醇为165mg,仅是联邦德国人的三分之一。     

Broad-Spectrum Antimalarial Activity of Peptido Sulfonyl Fluorides,a New Class of Proteasome Inhibitors

Despite declining numbers of cases and deaths, malaria remains a major public health problem in many parts of the world. Today, case management relies heavily on a single class of antimalarial compounds: artemisinins. Hence, development of resistance against artemisinins may destroy current malaria control strategies. Beyond malaria control are elimination and eradication programs that will require drugs with good activity against acute infection but also with preventive and transmission-blocking properties. Consequently, new antimalarials are needed not only to ensure malaria control but also for elimination and eradication efforts. In this study, we introduce peptido sulfonyl fluorides (PSF) as a new class of compounds with antiplasmodial activity. We show that PSF target the plasmodial proteasome and act on all asexual stages of the intraerythrocytic cycle and on gametocytes. PSF showed activities at concentrations as low as 20 nM against multidrug-resistant and chloroquine-sensitive Plasmodium falciparum laboratory strains and clinical isolates from Gabon. Structural requirements for activity were identified, and cytotoxicity in human HeLa or HEK 293 cells was low. The lead PSF PW28 suppressed growth of Plasmodium bergheiin vivo but showed signs of toxicity in mice. Considering their modular structure and broad spectrum of activity against different stages of the plasmodial life cycle, proteasome inhibitors based on PSF have a great potential for further development as preclinical candidate compounds with improved species-specific activity and less toxicity.     

Comparative Analysis of the Oxygen Supply and Viability of Human Osteoblasts in Three-Dimensional Titanium Scaffolds Produced by Laser-Beam or Electron-Beam Melting

Synthetic materials for bone replacement must ensure a sufficient mechanical stability and an adequate cell proliferation within the structures. Hereby, titanium materials are suitable for producing patient-individual porous bone scaffolds by using generative techniques. In this in vitro study, the viability of human osteoblasts was investigated in porous 3D Ti6Al4V scaffolds, which were produced by electron-beam (EBM) or laser-beam melting (LBM). For each examination, two cylindrical scaffolds (30 mm × 10 mm in size, 700 µm × 700 µm macropores) were placed on each other and seeded with cells. The oxygen consumption and the acidification in the center of the structures were investigated by means of microsensors. Additionally, the synthesis of pro-collagen type 1 was analyzed. On the LBM titanium scaffolds, vital bone cells were detected in the center and in the periphery after 8 days of cultivation. In the EBM titanium constructs, however, vital cells were only visible in the center. During the cultivation period, the cells increasingly produced procollagen type 1 in both scaffolds. In comparison to the periphery, the oxygen content in the center of the scaffolds slightly decreased. Furthermore, a slight acidification of the medium was detectable. Compared to LBM, the EBM titanium scaffolds showed a less favorable behavior with regard to cell seeding.     

Theophylline is able to partially revert cachexia in tumour-bearing rats

ABSTRACT: Background and aims: The aim of the present investigation was to examine the anti-wasting effects of theophylline (a methylxantine present in tea leaves) on a rat model of cancer cachexia. Methods: the in vitro effects of the nutraceuticals on proteolysis were examined on muscle cell cultures submitted to hyperthermia. Individual muscle weights, muscle gene expression, body composition and cardiac function were measured in rats bearing the Yoshida AH-130 ascites hepatoma, following theophylline treatment. Results: Theophylline treatment inhibited proteolysis in C2C12 cell line and resulted in an anti-proteolytic effect on muscle tissue (soleus and heart), which was associated with a decrease in circulating TNF-alpha levels and with a decreased proteolytic systems gene expression. Treatment with the nutraceutical also resulted in an improvement in body composition and cardiac function. Conclusion: Theophylline - alone or in combination with drugs - may be a candidate molecule for the treatment of cancer cachexia.